caa a22 4500 475771486 CHVBK 20180406123618.0 cr unu---uuuuu 170329e20000701xx s 000 0 eng 10.1007/s001250051466 doi (NATIONALLICENCE)springer-10.1007/s001250051466 Susceptibility to diabetes is widely distributed in normal class IIu haplotype rats [Elektronische Daten] [K. E. Ellerman, A. A. Like] Abstract : Aims/hypothesis. We did experiments to explore the pathways putatively leading to Type I (insulin-dependent) diabetes mellitus, and their association with the MHC locus, the major genetic determinant of disease susceptibility.¶Methods. Normal MHC congenic rat strains that do not spontaneously develop diabetes or any other autoimmune syndrome were injected with the interferon-alpha inducer polyinosinic-polycytidylic acid (Poly IC).¶Results. Insulitis and diabetes developed only in strains expressing Class IIu genes and was independent of the Class I haplotype. Poly IC induced islet cell Class I hyperexpression, up regulation of pancreatic endothelial intercellular adhesion molecule-1 and vascular adhesion molecule-1 and a T-cell and macrophage infiltration of the pancreatic interstitium in all rat strains studied, including diabetes-resistant strains. Poly IC also induced the generation of diabetes-transferring spleen cells in most Class IIu haplotype rats, including the diabetes-resistant WF rat.¶Conclusion/Interpretation. The minimum requirements for autoimmune diabetes development in the rat include: RT1 Class IIu genes, a T-cell repertoire containing beta-cell autoreactive T cells and a triggering event which breaks tolerance by the local up regulation of pancreatic endothelial adhesion receptors. Even when all of the minimum requirements have, however, been met, most Class IIu rats do not develop diabetes in response to autoimmune stimuli. It is clear, nonetheless, that susceptibility to diabetes is widely distributed in the RT1 u rat. [Diabetologia (2000) 43: 890-898] Springer-Verlag Berlin Heidelberg, 2000 Keywords Autoimmunity, BB rat, MHC Class II, adhesion molecules nationallicence Ellerman K. E. Department of Pathology, University of Massachusetts Medical School, Worcester, Mass., USA, US aut Like A. A. Department of Pathology, University of Massachusetts Medical School, Worcester, Mass., USA, US aut https://doi.org/10.1007/s001250051466 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051466 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ellerman K. E. Department of Pathology, University of Massachusetts Medical School, Worcester, Mass., USA, US aut NATIONALLICENCE 700 1- Like A. A. Department of Pathology, University of Massachusetts Medical School, Worcester, Mass., USA, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer